Exposure of skin to ultraviolet (UV) radiation induces a spectrum of cellular and clinical changes. Action spectra studies have revealed some of these changes to be highly inducible by UVC (or UVB), whereas other changes are inducible by UVA. On this basis, we hypothesize UV radiation of different wavelengths to cause activation of distinct signaling pathways and/or distinct sets of genes. Our objective is to develop an experimental model for studying signal transduction and gene activation induced by UV in human keratinocytes (KC). Specific aims are: 1) To identify the marker genes selectively activated by UV of different wavelengths. Human transformed KC (A431) will be exposed to UVA, UVB, or UVC, and examine for rapid expression of mRNA for different immediate-early genes. 2) To determine the responsive element(s) in promoter regions that is responsible for marker gene activation by different UV wavelengths. Responsive elements will be assessed by constructing different deletion mutants of the promoter regions and subcloning them into CAT vectors. 3) To identify the signaling pathways activated by different UV wavelengths that lead to marker gene expression. We will employ inhibitors and stimulators of known signal transduction pathways to block and induce UV-induced marker gene expression. These studies should provide a clearer understanding of the basic mechanisms responsible for UV-induced changes at molecular, cellular and even clinical levels. Knowledge derived will be applied to future work aimed at better characterizing the pathways for UV-activated gene regulation and at identifying the putative UV receptors in KC.